Sensing gas bubbles in a living body

ABSTRACT

A method of detecting gas bubbles in a living body, comprising transmitting at least one original electromagnetic signal to a body portion; detecting a signal modulated by a flow of blood in said body portion; and analyzing a perturbation in said signal to determine at least one of an existence and a property of a bubble in said blood flow.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.10/526,428, filed on Feb. 28, 2005, which is a National Phase of PCTPatent Application No. PCT/IL2003/000707, filed on Aug. 28, 2003, whichclaims the benefit of priority under 35 USC 119(e) of U.S. ProvisionalPatent Application No. 60/406,332, filed on Aug. 28, 2002.

The contents of all of the above applications are incorporated byreference as if fully set forth herein.

FIELD OF THE INVENTION

The present invention relates to sensing gas bubbles in a living body.

BACKGROUND OF THE INVENTION

Various gases are dissolved in the circulatory blood system of livingbodies. Changes in ambient pressure can lead to dispersion of gasbubbles from the liquid. At slow pressure changes, the body can expelthe bubbles. However at a high rate of change the body cannot expel themfast enough and they can accumulate or grow. Detection of gas bubbles ina living body, at an early stage of accumulating would allow treatmentbefore it is too late. As an example, people moving quickly from a placeof high atmospheric pressure to low atmospheric pressure, would beinterested in accurate monitoring of their situation in order to safelycontrol the rate of change. For example, underwater divers usestatistical tables to determine the rate at which they can surface froma deep dive instead of measuring their actual physical state. Whiledevices have been described for detection of bubbles in blood, forexample in U.S. Pat. No. 6,261,233, the disclosure of which isincorporated herein by reference, which describes an ultrasound system,such devices have apparently not found actual use, especially inunderwater situations.

SUMMARY OF THE INVENTION

An aspect of some embodiments of the invention relates to detecting andmonitoring gas bubbles within living bodies, based on perturbations in asignal received from a blood flow in the body in which the bubbles areextant and which bubbles cause the perturbations. In an exemplaryembodiment of the invention, a living body is radiated, using anelectromagnetic wavelength, transparent to the tissue or conduitencasing a fluid (e.g. blood) comprising gas bubbles. The waves aremodulated by the flow and are then received and analyzed, for example,to detect perturbations in the expected received signal. Optionally,analysis of the perturbations allows determining the size, rate ofgrowth and/or concentration of the gas bubbles and/or rate of flow ofthe blood.

In some embodiments of the invention, the measured signal is analyzedbased on the amplitudes of the measured signal. Alternatively oradditionally, the measured signal is analyzed based on the change infrequency between the transmitted wave and measured wave.

In some embodiments, an optical wave, for example, IR is used, at one ormore frequencies. In others, a different wave, for example, visual or RFis used.

It should be noted that electromagnetic wavelengths may be preferred formany uses, for example, underwater, due to the better controllability ofthe beam, due to the ability to using a coherent signal and/or detectionand/or due to the ability of using polarized beams and waves with acontrolled bandwidth and/or controlled spatial and temporal profile. Notall of these possibilities are utilized in every embodiment. However, insome cases, the methods described herein may be used for ultrasonicwaves. In such waves, frequency processing may be at the level of thepulse rate and/or at the level of actual changes in detectedfrequencies.

An aspect of some embodiments of the invention relates to real-timeprovision of monitoring and/or measurement of physiological parameters,in a wide range of situations, for example, underwater, on land and inair or space. Alternatively or additionally to measuring perturbations,other physiological parameters of the body may be detected (and/orchanges monitored) from analyzing the waves received from the blood, forexample, heart rate, pulse form, respiratory rate, blood pressure,cardiac output, Oxygen saturation (e.g., based on differentialabsorption at different wavelengths) and blood flow rate and/or volume.In some cases, determining changes in these parameters even for a signalorgan provides useful information about the physiological state of thewhole body. In an exemplary embodiment of the invention, a gauge fortracking and optionally displaying and or alerting a user is provided.In an exemplary embodiment of the invention, such a gauge is worn by theuser on his wrist and tracks bubble information and/or otherphysiological parameters. Optionally, the gauge can be worn by theperson on the wrist, leg, ankle, neck, or chest or on any other part ofthe body. In some embodiments of the invention the gauge can be used insevere conditions for example, underwater or in outer space.

In an exemplary embodiment of the invention, the gauge is used toprovide real-time physiological feedback, for example, underwater sothat there is no need to rely on statistical tables to predict thephysiological state of a person underwater. Rather, the exactprogression for a particular person under particular conditions can betracked. Possibly, the gauge learns the progression pattern for aperson, type of person, starting state and/or planned assignment (e.g.,fitness state, starting heart rate and/or other physiologicalparameters) and uses this pattern to predict problems in a dive. In oneembodiment, a statistical progression is calibrated in real-time, forexample, times of the progression extended or contracted based on thereal-time response of the person doing the activity.

There is thus provided in accordance with an exemplary embodiment of theinvention, a method of detecting gas bubbles in a living body,comprising:

transmitting at least one original electromagnetic signal to a bodyportion;

detecting a signal modulated by a flow of blood in said body portion;and

analyzing a perturbation in said signal to determine at least one of anexistence and a property of a bubble in said blood flow. Optionally,said original signal comprises a series of pulses. Alternatively oradditionally, said detected signal comprises a reflected signal.Alternatively or additionally, said detected signal comprises a signalmodulated by transmission through said flow. Alternatively oradditionally, said signal comprises a narrow bandwidth signal.Alternatively or additionally, said signal is visible light.Alternatively, said signal is infra-red light.

In an exemplary embodiment of the invention, said signal is at awavelength which is selectively absorbed by hemoglobin. Alternatively oradditionally, said signal is at a wavelength which is selectivelyreflected by blood vessel walls.

In an exemplary embodiment of the invention, said detected signal isdetected using multiple detectors. Alternatively or additionally, saidoriginal signal comprises multiple original signals from multiplesources. Optionally, said sources are arranged around a body part inwhich said bubbles are to be detected. Alternatively or additionally,said sources are arranged to view multiple parts of a body.Alternatively or additionally, said signals are detected in series.Alternatively or additionally, said signals have different wavelengths.Optionally, at least two of said different wavelengths have differentabsorption properties in blood.

Alternatively or additionally, analyzing comprises combing the effectsof said multiple sources.

In an exemplary embodiment of the invention, the method comprisesperforming AM on said detected signal. Optionally, said AM analysiscomprises estimating an unperturbated signal and counting zero crossingsrelative to said estimation. Optionally, said estimation is selected topreclude the detection of perturbations below a certain threshold.Alternatively or additionally, said estimation comprises an adaptivethreshold. Alternatively or additionally, said estimation reduces theeffect of systolic-caused changes in said signal.

In an exemplary embodiment of the invention, the method comprisesperforming FM on said detected signal. Optionally, the method comprisescombining said AM analysis and said FM analysis.

In an exemplary embodiment of the invention, the method comprisesperforming FM on said detected signal. Optionally, said FM analysiscomprises applying a frequency transform to said detected signal.Alternatively or additionally, said FM analysis comprises detectingchanges in a delay time of a said detected signal relative to saidoriginal signal. Alternatively or additionally, said FM analysiscomprises detecting a change in amplitude of a frequency component.

In an exemplary embodiment of the invention, the method comprisesanalyzing said received signal to determine a value or a change in aphysiological parameter other than bubbles. Optionally, saidphysiological parameter comprises a heart rate. Alternatively oradditionally, said physiological parameter comprises an oxygensaturation. Alternatively or additionally, said physiological parametercomprises a respiration rate.

In an exemplary embodiment of the invention, said analyzing comprisesestimating a number of bubbles. Alternatively or additionally, saidanalyzing comprises estimating a volume of bubbles. Alternatively oradditionally, said analyzing comprises tracking the formation of atleast one bubble. Alternatively or additionally, said analyzingestimating a diameter of at least one bubble.

In an exemplary embodiment of the invention, the method comprisesestimating a physiological state for diving purposes based on saidanalysis.

In an exemplary embodiment of the invention, transmitting comprisestransmitting when in contact with a skin surface. Alternatively,transmitting comprises transmitting through a layer of water.Optionally, said layer is between 1 and 20 mm thick.

There is also provided in accordance with an exemplary embodiment of theinvention, a method of detecting gas bubbles in a living body,comprising:

transmitting at least one original signal to a body portion;

detecting a signal modulated by a flow of blood in said body portion;and

analyzing, using AM analysis, a perturbation in said signal to determineat least one of an existence and a property of a bubble in said bloodflow. Optionally, said signal comprises an ultrasonic signal.Optionally, the method comprises applying an FM analysis.

There is also provided in accordance with an exemplary embodiment of theinvention, apparatus for bubble detection, comprising:

at least one electromagnetic signal source adapted to transmit a waveinto a body;

at least one sensor adapted to receive said signal after modulation by aflow in said body; and

circuitry adapted to analyze said received signal and detect thepresence of a bubble in said flow. Optionally, said circuitry is adaptedto self-calibrate said apparatus. Alternatively or additionally, saidcircuitry is adapted to detect if a placement of said device issuitable. Alternatively or additionally, said device is adapted to beworn on a wrist. Alternatively or additionally, said device is adaptedfor underwater use during diving.

In an exemplary embodiment of the invention, said apparatus comprises awireless link. Alternatively or additionally, said apparatus comprises auser input for providing task related information.

There is also provided in accordance with an exemplary embodiment of theinvention, apparatus for physiological tracking bubble detection,comprising:

at least one electromagnetic signal source adapted to transmit a waveinto a body;

at least one sensor adapted to receive said signal after modulation by aflow in said body; and

circuitry adapted to analyze said received signal and detect at leastchanges in at least two physiological parameters of said body.Optionally, said at least two physiological parameters are selected froma group comprising, existence of bubbles, heart rate, respiration rate,blood pressure, oxygen saturation and vascular response.

There is also provided in accordance with an exemplary embodiment of theinvention, a method of bubble tracking in a living body, comprising:

transmitting at least one original signal to a body portion;

detecting a signal modulated by a bubble in said body portion; and

analyzing a perturbation in said signal to determine at least one of anexistence and a change in size of a bubble in said body portion.

BRIEF DESCRIPTION OF FIGURES

Particular exemplary embodiments of the invention will be described withreference to the following description of embodiments in conjunctionwith the figures, wherein identical structures, elements or parts whichappear in more than one figure are generally labeled with a same orsimilar number in all the figures in which they appear, in which:

FIG. 1 is a schematic illustrations of a detection device and its useaccording to an exemplary embodiment of the invention;

FIG. 2 is schematic block diagram of a circuit for the detection deviceof FIG. 1, in accordance with an exemplary embodiment of the invention;

FIG. 3A, 3B, 3C and 3D are schematic graphs, illustrating the amplitudeof transmitted waves and detected wave, in accordance with an exemplaryembodiment of the invention;

FIG. 3E shows the effect of a breathing cycle on the measured signal;

FIG. 4 is an illustration of two schematic graphs, illustrating the timedomain of transmitted waves and detected waves, in accordance with anexemplary embodiment of the invention;

FIG. 5 is a flow diagram of the process of detecting gas bubblesaccording to an exemplary embodiment of the invention;

FIGS. 6A and 6B are schematic illustrations of a detection device andits deployment according to an exemplary embodiment of the invention;and

FIG. 6C is a schematic illustration of a detection device deployed inaccordance with an alternative embodiment of the invention.

DETAILED DESCRIPTION OF EMBODIMENTS General Structure

FIG. 1 is a schematic illustration of a gas bubble detection device 100,according to an exemplary embodiment of the invention. Detection device100 transmits an original signal 170, for example a visible light beamtoward a living body 220. A sensor 120 in detection device 100 detectsand analyses a reflected signal 180. Sensor 120 optionally includes anarrow-bandwidth filter. In some embodiments of the invention, atransmitted signal 190, that passes through body 220 is analyzed insteador in addition. In an exemplary embodiment of the invention, theanalyses compares original signal 170 and the received signal. In anexemplary embodiment of the invention, perturbations in sensed signalare analyzed to yield information about gas bubbles 210 found in a flowof blood or other body fluids and/or in non-flowing tissues.

As will be described below various types and wavelengths of waves can beused for signal 170, including, for example, RF, ultrasound and IR. Inan exemplary embodiment of the invention, one or more sources 110 areprovided for signal 170, for example one or more lasers or LED diodes,which emit signal 170. It should be noted that coherent light is notrequired in some embodiments and in other embodiments, a relatively widebandwidth of light, rather than a narrow bandwidth of light, may beused. Also, while a beam is used in some embodiments, in otherembodiments, signal 170 may be spread out, patterned and/or focused to acertain area.

In an exemplary embodiment of the invention, signal 170 is radiatedtoward a conduit 200, for example a blood vessel (e.g. vein or artery).In an exemplary embodiment of the invention, signal 170 is of a typeand/or wavelength which passes substantially unattenuated (or onlypartially attenuated to a fixed degree) through tissue of the livingbody. Optionally, signal 170 wave is reflected from blood and alsoreflected by gas bubbles. Alternatively or additionally, signal 170penetrates blood but is absorbed or scattered by gas bubbles.Alternatively, signal 170 penetrates gas bubbles but is absorbed orscattered by blood. Differential effects of the blood and bubbles onsignal 170 are optionally used as described below. Also, differentialeffects for different wavelengths may be used, for example as describedbelow. In some embodiments of the invention, the effect on the signal bymovement of the blood and/or gas bubbles is used.

In some embodiments of the invention one or both of the followingeffects are used: differences in amplitude caused by existence of gasbubbles and differences in frequency shifts or profiles caused byexistence of gas bubbles. It is noted that in some embodiments thegrowth of gas bubbles can be detected, possibly even in stationarytissue.

In an exemplary embodiment of the invention, the sensed signal exhibitsa generally sinusoidal shaped graph, representing the systolic wave ofthe living body. However, as noted below, this general shape may beanalyzed to determine additional information. Further, for perturbationanalysis, a moving threshold or frequency filter may be used whicheffectively hides the generally sinusoid shape.

In some embodiments of the invention, signal sensor 120 comprises anelectromagnetic sensor such as a photodiode, PIN diode or a CCD.Optionally, sensor 120 is connected to an electronic circuit 140, whichanalyzes the sensed signal. The results are then optionally displayed toa user on a display 150 or as an audio signal on a speaker 160, forexample by a series of beeps or a voice speaking out values.

FIG. 2 is schematic block diagram of a circuit 140 according to anexemplary embodiment of the invention. In an exemplary embodiment of theinvention, circuit 140 comprises a processor 510 which controls thedevice and analyzes the sensed signals. Separate processor or othercircuit types may be used instead. Circuit 140 receives measurements ona communication interface 530 from sensor 120, for example using anexternal cable 130, an internal bus and/or using a wireless connection.While interface 530 is optional, it may be used to reject some signalsor for communicating with sensor 120. An analog to digital converter 540converts the received signal, optionally only if the signal is within agiven range.

In an exemplary embodiment of the invention, circuit 140 comprises apower source 550 (e.g. a battery) to supply power for detector 100.Optionally, the device has a user input 560 (e.g. a switch) to turndetection device 100 on and off, and optionally, select modes ofoperation, for example display modes for display 150 or for selectingsensed physiological parameters.

In an exemplary embodiment of the invention, device 100 comprises anoutput interface 570, which controls output to display 150, speaker 160and other outputs, such as an interface to an external computer using aUSB connection, wireless connection (e.g., BlueTooth), serial connectionor parallel connection. In some embodiments of the invention, device 100is used for remote monitoring of the physiological state of a person(e.g. in a dangerous environment).

In some embodiments of the invention, circuit 140 comprises a directbody interface, for example an electric shock device or pricking deviceto arouse a person's attention in case of deterioration of theirphysical state.

Amplitude Analysis

In an exemplary embodiment of the invention, detection device 100applies amplitude analysis on the reflected signal 180 and/ortransmitted signal 190 (i.e., sensed signals) to determine the existenceof gas bubbles and provide other physiological parameters as describedbelow.

FIGS. 3A, 3B, 3C and 3D are schematic graphs, illustrating the amplitudeof the original signal and the sensed signal, in accordance with anexemplary embodiment of the invention.

In an exemplary embodiment of the invention, original signal 170 istransmitted as a series of short pulses of a fixed amplitude, at aselected rate (for example, 1 Mz) from one or more sources into theliving body. Graph 250 of FIG. 3A shows the amplitude of the originalsignal 170 as a function of time. Other pulse frequencies may be used aswell, for example in the range of 100 kHz to 6 GHz. As noted below, theamplitude may be non-constant.

Graph 260 of FIG. 3B shows a sensed signal (e.g., 180 in FIG. 1) as afunction of time. In an exemplary embodiment of the invention, asexplained above the resulting measured amplitudes render a generallysinusoidal shaped graph. It is expected that the generally sinusoidalshaped graph comprises small perturbations from a smooth systolic wavedue to the effect of gas bubbles 210. Other possible sources of suchperturbations include noise and movement artifacts.

Graph 270 is a magnified view of a short segment 266 of graph 260. Themagnified view reveals the perturbations to the amplitude of thesystolic wave some of which are caused by the existence of gas bubbles.

Graph 280 shows the perturbations in graph 270 of FIG. 3C normalizedrelative to the systolic wave in order to simplify the explanation andgenerally in accordance to the effect of using a moving threshold asdescribed below.

What is described now is for the case where reflection (typicallyscattering) from a gas bubble is greater than that for blood. A similarbut modified analysis may be used for opposite cases or for transmittedsignals.

The amplitude at a specific time in graph 280 is affected by theexistence of one or more bubbles and may be proportional to the size ofthe bubbles at the measured point. Alternatively, the total area betweentwo zero crossings may be related to the bubble size. The change in timeof the amplitude illustrates the gas bubble flow at the point beingmeasured. In some embodiments of the invention, a bubble increases themeasured amplitude, for example the amplitude measured from a reflectedwave 180. In some embodiments of the invention, a bubble reduces themeasured amplitude, for example in measuring a transmitted wave, whichis weakened by passing through the bubble in passing through body 220.

It should be noted that the effect of bubble size and/or number may benon-linear with regard to number and/or volume. It should also be notedthat in case the bubbles are uniform and dense in the blood flow, it ispossible that the perturbations may be smaller than if there are fewerbubbles or the bubbles be undetected. However, for physiologicalreasons, once the bubbles are substantially uniform in the blood, thepatient is in grave danger, if not already dead. It should also be notedthat the formation of a new bubble in a clear blood flow will alsogenerally cause a perturbation. It is expected that the perturbationsdetected grow (even if not linearly) from the point where there is nodanger at least until a danger point beyond which an exact measurementis not really useful. In any case, the detection device can becalibrated for different conditions and even be calibrated todifferentially detect a small number of perturbations when the totalreflectance is large (signifying many bubbles) than when the totalreflection is lower (signifying fewer bubbles). Additionally, otherprocessing methods as described below may be used.

In an exemplary embodiment of the invention, a measured amplitude may beincorrect due to noise in the system. A low amplitude value may be aresult of noise and not related to gas bubbles, whereas a high amplitudevalue would probably be at least in part related to gas bubbles.Optionally, a threshold value is selected in order to limit the analysisto larger amplitude values which are clearly related to bubbles. In FIG.3C and FIG. 3D a threshold line K is passed through graphs 270 and 280respectively.

Typically the threshold value is selected to leave 80% of the measuredamplitudes above line K. Optionally, this value is continuously updatedby taking into account the average deviation of the amplitudes in thegraph from this value, resulting in the majority of points being abovethe threshold. Points on the graph that cross line K are referred to ascrossing points, for example points 282 and 284 in graph 280 of FIG. 3D.The crossing points mark the beginning and end of a gas bubble (or groupof bubbles) of sufficient size to be taken into account. The number ofbubbles over a specific time is equal to half of the number of crossingpoints over that time. In some embodiments of the invention, two or moresmaller bubbles may be referred to as one larger bubble, if theresulting amplitudes are not accurate enough to differentiate. In somecases, as described below, viewing form multiple angles, for example,90, 280, 270 or more, such as 350 or 360 may be used. The number oftransmitted pulses between two crossing points result in a valueproportional to the volume of the bubble (W). In an exemplary embodimentof the invention, the use of an adaptive threshold causes the thresholdline to follow the systolic wave, thereby eliminating its effect.Alternatively or additionally, frequency filtering techniques may beused.

In some case, what is determined is the diameter of the bubble, whichmay be dependent on the amplitude of the perturbation. Changes in thisdiameter, for example at several points along the flow, or as a functionof time, may be an indication of bubble growth. Total bubble volume maybe provided in some cases by integrating the positive portion of theperturbations over a item period.

In some embodiments the minimum size of a bubble which can be detectedis dictated by the wavelength used, for example, to be more than 0.5*0.3microns, for an 0.3 micron wavelength.

It should be noted that depending on the signals used and area beingsensed what may be measured is actually groups of bubbles rather thansingle bubbles. However, if only simple assumptions are made about thebubble distribution, for example that the bubbles act in a statisticallyregular manner (e.g., even random distribution), the number of groups ofbubbles and their sizes are expected to correlate with the physiologicalstate. It should also be noted that statistical analysis of the “volume”of the bubbles may also be used to help count bubbles, by assuming(e.g., based on calibration tests) a certain distribution and correctingfor it.

It should be noted that the area being viewed by sensor 120 andilluminated by signal 170 may encompass more than one blood vessel.furthermore, as described below, signals may be purposely detected fromdifferent sized blood vessels and/or static tissue. In each suchdetected signal, the above described processing may be applied albeit,optionally with different calibration.

This analysis allows detecting bubbles. Additionally, this analysisgives an approximation to the number and/or volume of bubbles in a timeperiod and/or flow volume (if blood flow volume is also estimated).

Frequency Analysis

FIG. 4 shows two schematic graphs 350 and 360, illustrating the timedomain of transmitted waves and detected waves, in accordance with anexemplary embodiment of the invention.

Graph 350 of FIG. 4 shows the amplitude versus time of the pulses oftransmitted electromagnetic wave 170. Graph 360 of FIG. 4 shows theamplitude of the pulses of the measured electromagnetic wave (180, 190)as a function of time, for one exemplary embodiment of the invention.The comparison of graph 360 with graph 350 shows a shift in thereception time of the received pulses relative to their expectedreception time. This shift depends on the speed of the reflectingobject, in that different speeds generate different time shifts. Itshould be appreciated that blood flows at a range of distances and at arange of speeds, thus providing a certain profile of time shifts.However, a bubble, reflects a significantly greater amount of energy (insome embodiments) and/or may move at a different speed than the rest ofthe flow, thereby changing the frequency profile of the reflection.

The frequency shift is a result of the Doppler effect caused by samplingthe moving blood flow and gas bubbles. In addition, newly formed bubblesare also visible. A gas bubble may precipitate from the blood flow as aresult of changes in the ambient pressure on the blood vessel, tissueand/or for other reasons. The gas bubble initially clings to the wallsof the blood vessel and then accelerates with the blood flow until itreaches the speed of the blood flow. In an exemplary embodiment of theinvention, analysis of the frequency shift reveals a sinusoidal patternof growing and diminishing shift size. Optionally, the accelerating gasbubbles 210 cause perturbations to this simple pattern. Alternatively oradditionally, existing bubbles can cause turbulence and/or change theirspeed, such as when they bounce into wall, cling momentarily and/orotherwise move erratically. Alternatively or additionally, it is notedthat blood flow in arteries is pulsate in general and the blood mayaccelerate with each pulse at a different speed form the bubbles.

In an exemplary embodiment of the invention, time shift analysiscomprises noting changes in the reflection time for one or more pulsesand/or performing statistical analyses on them. Alternatively oradditionally, a frequency transform, such as Fast Fourier Transform(FFT) or a Wavelet Transform are performed on the signal. The result isa frequency profile which, as noted above, can be expected to change asa function of the bubbles. In some embodiments, what is analyzed is notchanges in the frequency profile but rather the amplitude of thedifferent frequencies, for example a spike in a certain frequency canindicate a sudden large reflection of an object (e.g., a bubble) at acertain speed. Counting such spikes can give an indication of a numberof bubbles and/or be used to correct the amplitude analysis for theeffects of noise.

It should be noted that the results from different analysis types may becombined, for example, using AM analysis to detect when a bubble existsand FM analysis to determine its size and/or abnormal propagation.

Determining Other Information from the Measured Signals

Alternatively or additionally, other physiological parameters and/orchanges therein of living body 220, may be determined from the sensedsignal, for example systolic wave, blood pressure, heart rate, cardiacoutput, respiratory rate, possibly an indication of respiratory capacityor changes therein and vascular resistance. Following are detailsexplaining how these physiological parameters can be determined from themeasurements of device 100.

Graph 260 of FIG. 3 optionally, shows the systolic wave. The extremepoints (e.g. 262 and 264) of the systolic wave (in graph 260)optionally, show the change in blood pressure, for example passing fromhigh to low between point 262 to 264. The number of maximum points (e.g.point 262) over a period of time optionally, give the heart rate.Integration between two points on graph 260 optionally, gives thecardiac output of the measured point over the selected time. While acomplete cardiac output requires monitoring all the blood flow, forexample at the aorta, changes in the flow to an organ, such as the hand,may correlate with various physiological conditions, such as reducedcardiac output, shock, or extreme exercise.

In an exemplary embodiment of the invention, the respiratory rate isalso available from the measured wave shown in graph 260. As describedabove, the systolic wave is the carrier for the gas bubble perturbations(graph 270). Likewise the systolic wave is a modulation of a respiratorywave which forms a somewhat sinusoidal base for the systolic wave, asshown in a graph 290 of FIG. 3E. Suitable spatial filtering of thesensed signal will provide the respiratory rate. For example, thesystolic rate is between 5 and 300 pulses per minute and the respiratoryrate is between 2 and 0.1 pulses per second An estimate that is somewhatcorrelated with the respiratory capacity is determined by integratingover the respiratory wave.

The systemic vascular resistance (SVR), which is the resistance to theblood flow is optionally determined by rate of change of the slope ofthe systolic wave (dP/dt for a point P′). With:

SVR=E*P′/(dp/dt), E=(dp/dt)dt for a point p′

SVR=rate of change*pressure at point/slope

A blood pressure may be measured using an oscillometric method.Alternatively or additionally, changes in blood pressure are monitored.Alternatively or additionally, a calibration value may be measured priorto use, for example using a standard blood pressure measurement device.

In some embodiments of the invention, detection device 100 allows a userto select the physiological parameters that will be analyzed, forexample using user input 560. In some embodiment of the invention,detection device 100 can analyze interrelated parameters to determine ausers condition and/or verify integrity of the measurements. In anexemplary embodiment of the invention, one or more rules or formula areprogrammed into device 100 to describe the relationship betweenphysiological parameters. Alternatively or additionally, a user may berequired to enter one or more values, for example, physical fitness ordegree of prior exercise. In an exemplary embodiment of the invention,device 100 may be used to monitor physiological parameters of the bodyand indicate where certain action, such as pausing assent in diving,should be taken or is imminent. While device 100 may utilize standardtime based table, in an exemplary embodiment of the invention, device100 relays at least in part on actual physiological measurements, suchas detection of bubbles or reduction in cardiac output instead of or inaddition to such standard tables.

Optionally, the user can select, which parameter or parameters will bedisplayed and/or the method of display, for example a graph, a singlechanging value, an audio message or sound and/or direct stimulation, forexample electrical or tactile stimulation.

In some embodiments of the invention, specific parameters can beselected to give an alert to the user (or to a remote user, for example,via an umbilical cable) on specific “higher level” states, for example,stress which can be identified by high pulse rate, high respiratoryrate, and change in systolic rate or cardiac output. Stress is just oneexample of states that can be defined based on the interaction ofmultiple parameters and/or integration of multiple parameters. Inparticular, it is noted that changes in one parameter may modify themeaning of other parameters, for example, a reduction in respiratoryrate may reduce oxygen saturation on its own even without additionalfactors and thus, is optionally used to correct the interpretation ofthe oxygen saturation parameter.

Exemplary Method of Utilization

FIG. 5 is a flow diagram 400 of the process of detecting gas bubblesaccording to an exemplary embodiment of the invention. Detection device100 transmits (410) a signal (170, FIG. 1) to measure a flow of gasbubbles 210 in living body 220. Detection device 100 receives (420) asignal (180, FIG. 1) reflected from the blood flow in body 220. In someembodiments of the invention, the received signal is used to initially(and/or later and/or periodically) adjust the transmitted signal. Insome embodiments of the invention, the measured signal is analyzed todetermine if it conforms to a basic form. If the signal does not conformto the basic form, this may indicate in correct placement of the deviceand/or incorrect signal parameters. Optionally (480) calibrationinformation is sent to transmitter 110 and/or sensor 120.

The calibration information can adjust parameters such as one or moreof:

a. The frequency of the transmitting pulses, by raising or lowering thepulse rate, variable rate may be used.b. The amplitude of the transmitted pulses, by raising or lowering thepower supplied to the signal sources 110, variable amplitude may beused.c. The noise threshold, by raising the selected threshold value asdescribed above.d. The type of modulation, for example pulse CW, chirp, monopulse, AMand/or FM, which may instead be fixed.e. Selecting different sensors for sampling the signal, in an embodimentusing multiple sensors as described below.

In some embodiments of the invention, detection device 100 signals theuser to adjust the physical position of the sensor, for example afterfailing to receive an acceptable signal despite changing controllableparameters.

Optionally, if an analog signal is used it is converted 430 to a digitalsignal for processing. Alternatively, the receiver samples the receivedsignal directly as a digital signal using a digital sensor.Alternatively, analog processing may be provided.

In some embodiments of the invention, the digital information isanalyzed (440), for example to check that the information is a logicalmeasurement comprising meaningful information. Optionally, (440)prevents accepting illogical information, which can be caused forexample by detection device 100 being knocked out of position or anexternal flash of light.

In some embodiments of the invention, received measurements (and/ordetermined physiological data) that are not found to be faulty arestored (450) in memory 520. Optionally, the analysis in (440) isperformed on the current information and also takes into accountinformation stored in memory 520 (FIG. 2), for example to check that thecurrent measurements are logical in view of the previous measurements.

The information stored in memory is optionally used to calculate (460)physiological parameters, for example, the number of gas bubbles, thesize of the gas bubbles, the rate of flow of the gas bubbles, the growthin the rate of flow of bubbles and growth in the number of bubbles as afunction of time as described above. Calculated parameters are thenoutput (470) for the user to view, for example by showing the values ondisplay 150, or reading out the values on speaker 160, or flashing lightor beeping at a selected pace in order to pass on the information to theuser of the system. In some embodiments of the invention, a graph isshown on display 150 to illustrate the status of a selected parameter.Optionally, a user can select the parameter to be displayed, for exampleusing a selection button as described above.

If however the information during the analysis (440) is found to befaulty then the information is optionally analyzed by processor 510 todetermine if adjustments need to be made as described above.Alternatively or additionally, processor 510 will notify the user tocheck device 100 and fix the problem, for example by displaying amessage (460) on display 150 and/or speaker 160.

Other Embodiments

Optionally, the wavelength of the light is selected from wavelengths,which are not hazardous to the body, for example the LED diodes maytransmit light of wavelengths of 400-1500 nanometers, emitting lightthat is visible to the human eye or light that is non visible to theeye. Alternatively or additionally, a hazardous wavelength can beradiated at a very short pulse length with a momentary high energy,giving an average energy value close to zero so that there is minimalinteraction with body 220.

In some embodiments of the invention the wavelength is selectedaccording to the part of the body being analyzed, or the element that isof interest, for example a wavelength of 540 nanometers is specificallyaffected by Hemoglobin causing a sharper measured signal. Otherwavelengths, for example between 300 and 1500 nm, may be used. Inanother example, a wavelength of 810 nm shows the effect of the systolicwave by reflection from the body of the blood vessel and may be used,for example, to provide information about vascular compliance or aboutthe actual systolic wave form. A wavelength of 950 nm may be sensitiveto movement of the sensor, thus allowing movement artifacts to berecognized and ignored, in other wavelengths. A wavelength of 1100 nmmay show movement artifacts like the 950 nm wavelength, without acontribution of the outside of the movement of the blood vessel. Higherwavelengths may be useful for viewing into and through fat tissue.Oxygen saturation may be detected and/or monitored if severalwavelengths are used, for example as well known in the art. Suchsaturation monitoring may be especially useful for diving with abnormalpartial oxygen pressure and/or in general for detecting changes inOxygen saturation as a function of partial Oxygen pressure. Multiplewavelengths maybe also be used to determine the effect of interveningtissue, possibly transmitted in parallel or in series to each other.Alternatively or additionally, different wavelengths may have oppositeinteractions with blood and bubbles, for example one wavelength beingreflected by bubbles and another absorbed. Further, differentwavelengths may be used for transmission and for reflection. Multiplewavelengths may also be used for viewing different tissue depths, withdifferent wavelengths being capable of penetrating different amounts.The angles between the transmitter and receiver for such wavelengths maytake this distance into account. Also different wavelengths may be usedfor different body structures, for example larger blood vessels,arteries, veins and capillary tissue may use different wavelengths toassist differentiation. Multiple detectors may be used, or a singledetector may be shared. In one embodiment of the invention, a wavelengthwhich is not differentially affected by blood and tissue is used tocalibrate the signal levels.

In FIG. 1 sensor 120 is shown in the center of the light sources tosense reflected light 180, however sensor 120 may be positionedelsewhere such as opposite the light sources, on the other side ofliving body 220 in order to sense transmitted signals 190.

FIGS. 6A and 6B are schematic illustrations of a detection device andits deployment according to an exemplary embodiment of the invention. Insome embodiments of the invention, as shown in FIGS. 6A and 6B, multiplesensors (and/or multiple sources) are used, to allow device 100 toselect the sampling point, for example if a specific sensor does notgive acceptable results. Alternatively or additionally, device 100 cansense signals using multiple sensors 120 and optionally, average overthe results of several sensors or compare the results of differentsensors used on the same body. For example, 2, 3, 4 or more sensors maybe used. Alternatively or additionally, for example, 2, 3, 4 or moresources may be used.

Alternatively or additionally, the use of multiple sensors allows someshadowing artifacts to be overcome. Alternatively or additionally, arelatively large sensor is used which can detect light reflected frommultiple locations, possibly overcoming some shadowing effects as well.

While not shown, in some embodiments of the invention, the sources 110and/or sensor 120 may be physically aimed, for example manually using asmall screw and/or electrically using a motor. Scanning at differentangles may be used to establish a viewing area with sufficient bloodflow and/or blood flow of a desired type, such as veins, arteries and/orsmall vessels. Such scanning may be manual or automatic, depending onthe embodiment.

In an exemplary embodiment of the invention, as shown in FIG. 6Bmultiple sensors 120 are provided, which may sense reflected waves 180and transmitted waves 190 and/or sense waves scattered at variousscattering angles.

In some embodiments of the invention, source 110 and/or sensor 120 arepositioned so that the signal travels in a direction having a componentparallel to the direction of motion of gas bubbles 210, to betterprovide a Doppler effect. Alternatively or additionally, any Dopplershift in the perpendicular direction is from turbulence and/or anerratically moving bubble.

In some embodiments of the invention, the device is shaped as awristwatch (as shown in FIG. 6A) or a necklace (not shown), wherein allparts of the device are worn close to the body. Optionally, the lightsource and sensor are adhesively attached to body 220, for example usingtape. Alternatively, detection device 100 can be kept in place by astrap or band 175. A coupling gel is optionally provided to ensure goodoptical contact between device 100 and the skin. Alternatively, forexample underwater, measurement through the water, for example between0.1 and 10 cm, for example 2 cm, is provided. In some embodiments, thewater itself serves as a coupling layer and no separate gel layer isrequired. Alternatively, a layer of transparent silicone or othergel-like material is provided on the outside of device 100, to contactthe skin. Alternatively, tight attachment of device 100 to the bodysubstantially precludes the existence of a water layer between device100 and the body. Measurement through the air is also possible for somewavelengths, optionally using a coherent light source. for some types ofmaterials and/or wavelengths, measurement through clothes is alsopossible.

In some embodiments of the invention, electronic circuit 140 is attachedon the same band as sensor 120 or even in the same encasement as thelight sources 110 and sensor 120. Alternatively or additionally,electronic circuit 140 may be placed in a position with easy access forthe user, while the measuring part is placed where it can convenientlymeasure, for example electronic circuit 140 may be worn on a user'swrist and the light sources 110 and sensor 120 may be worn on a user'sstomach or ankle. Optionally, when initially, placing device 100, theuser is required to adjust its position until receiving a satisfactorysignal on the display. Alternatively or additionally, when usingmultiple sensors, a sensor with a good signal can be selected from amongthe sensors without needing to adjust the sensors. Alternatively, thesignals from multiple sensors and/or sources can be combined and/oraveraged. Optionally, sensor 120 is provided as a linear or 2D array ofsensors, rather than as a scalar sensor as in some embodiments.Different elements of the array may be adapted for differentwavelengths.

When contributions from multiple signals are combined, the combinationmay be, for example at the signal level, after sensing, after A/Dconversion and/or after processing. in some cases, the combination takesthe form of using one result to check the reliability of other results.It should be noted transmitted and reflected effects can be combined,for example, by averaging the bubble count of each.

FIG. 6C shows an embodiment where the circuitry of device 100 fits overclothes, while one or more sensors and/or light sources fit under thecloths, for example, as one or more clips 185. This embodiment may beused for a diving suit. Optionally, a small hole in the suit is providedfor a wire or the wire passes through a zipper area (not shown).

In some embodiments of the invention, detection device 100 is sealed ina protective encasement or prepared from parts that are water resistantand/or durable under high pressure, so that detection device 100 can beused under severe conditions, such as during diving underwater. In anexemplary embodiment of the invention, the protective construction ofdetection device 100, allows use of the device to measure physiologicalsigns and gas bubbles under water and/or in outer space. In analternative embodiment of the invention, device 100 is provided as acomponent of a dive computer to assist with the calculations indicatedby statistical tables.

In an exemplary embodiment of the invention, the device can be coupledto an external computer using output interface 570, for example using awired or wireless link.

In an exemplary embodiment of the invention, sensor 120 samples morethan one point and/or samples an area, this allows further confirmationof the accuracy of the measurements and/or allows to provide an average.Optionally, the relative measurement of flow between multiple sensedpoints along the path of conduit 200 allow calculation of the rate offlow of the bubbles and their density in the blood stream using AMmodulation and comparing between the points.

It should be noted that although in the above description reference ismade primarily to electromagnetic waves, other types of waves of variouswave-forms can be used, for example audio waves of various wavelengths(e.g. ultrasonic).

As noted above, calibration may be performed, for example, by taking ameasurement prior to diving or by comparing to the results of acalibrated device (e.g., using a computer link between the two devices).Alternatively or additionally, calibration is carried out aftermeasurement, for example in the middle or after a dive, and used toanalyze previously stored data. Alternatively or additionally, a lowerquality calibration is done in the field and a higher qualitycalibration is done in a laboratory. It is noted that for some uses allthat is required is monitoring of changes relative to the startingstate.

It will be appreciated that the above described methods may be varied inmany ways, including, changing the order of steps, and the exactimplementation used. It should also be appreciated that the abovedescribed description of methods and apparatus are to be interpreted asincluding apparatus for carrying out the methods and methods of usingthe apparatus.

The present invention has been described using non-limiting detaileddescriptions of embodiments thereof that are provided by way of exampleand are not intended to limit the scope of the invention. It should beunderstood that features and/or steps described with respect to oneembodiment may be used with other embodiments and that not allembodiments of the invention have all of the features and/or steps shownin a particular figure or described with respect to one of theembodiments. Variations of embodiments described will occur to personsof the art. Section titles are provided for clarity and do notnecessarily limit the contents of the section to the use of the title.

It is noted that some of the above described embodiments may describethe best mode contemplated by the inventors and therefore may includestructure, acts or details of structures and acts that may not beessential to the invention and which are described as examples.Structure and acts described herein are replaceable by equivalents whichperform the same function, even if the structure or acts are different,as known in the art. Therefore, the scope of the invention is limitedonly by the elements and limitations as used in the claims. When used inthe following claims, the terms “comprise”, “include”, “have” and theirconjugates mean “including but not limited to”.

1. A method of detecting gas bubbles in a living body, comprising:transmitting at least one original electromagnetic signal to a bodyportion; detecting a signal modulated by a flow of blood in said bodyportion; and analyzing a perturbation in said signal to determine atleast one of an existence and a property of a bubble in said blood flow.2. A method according to claim 1, comprising performing AM on saiddetected signal.
 3. A method according to claim 2, wherein said AManalysis comprises estimating an unperturbated signal and counting zerocrossings relative to said estimation.
 4. A method according to claim 3,wherein said estimation is selected to preclude the detection ofperturbations below a certain threshold.
 5. A method according to claim3, wherein said estimation comprises an adaptive threshold.
 6. A methodaccording to claim 3, wherein said estimation reduces the effect ofsystolic-caused changes in said signal.
 7. A method according to claim2, comprising performing FM on said detected signal.
 8. A methodaccording to claim 7, comprising combining said AM analysis and said FManalysis.
 9. A method according to claim 1, comprising performing FM onsaid detected signal.
 10. A method according to claim 9, wherein said FManalysis comprises applying a frequency transform to said detectedsignal.
 11. A method according to claim 9, wherein said FM analysiscomprises detecting changes in a delay time of a said detected signalrelative to said original signal.
 12. A method according to claim 9,wherein said FM analysis comprises detecting a change in amplitude of afrequency component.
 13. A method according to claim 1, comprisinganalyzing said received signal to determine a value or a change in aphysiological parameter other than bubbles.
 14. A method according toclaim 13, wherein said physiological parameter comprises a heart rate.15. A method according to claim 13, wherein said physiological parametercomprises oxygen saturation.
 16. A method according to claim 13, whereinsaid physiological parameter comprises one or both of a respiration rateand a respiratory capacity.
 17. A method according to claim 16, whereinthe physiological parameter comprises a respiration rate, anddetermining the value or change in the physiological parameter comprisesdetermining the respiration rate from a measured systolic wave.
 18. Amethod according to claim 13, wherein said physiological parametercomprises one or more of a wave form, pulse form, a cardiac output, ablood flow rate, a blood volume, a blood pressure, and a systemicvascular resistance.
 19. A method according to claim 18, wherein thephysiological parameter comprises a local blood flow rate to an organ,and the method also comprises using a change in the local blood flowrate to estimate a change in a physiological condition of the body as awhole.
 20. A method according to claim 13, wherein a user selects one ormore such physiological parameters.
 21. A method according to claim 20,also comprising displaying one or more such physiological parametersselected by the user.
 22. A method according to claim 21, comprisingusing a change in the physiological state to predict problems during adive, and to indicate where certain action should be taken or isimminent.
 23. A method according to claim 22, wherein the change in thephysiological state comprises one or more of appearance of bubbles,reduction in cardiac output, and increase in stress.
 24. A methodaccording to claim 22, wherein using the change in the physiologicalstate to predict problems comprises adapting the prediction to a persondoing the diving based on a real-time response of the person.
 25. Amethod according to claim 1, wherein said analyzing comprises estimatinga number of bubbles.
 26. A method according to claim 1, wherein saidanalyzing comprises estimating a volume of bubbles.
 27. A methodaccording to claim 1, wherein said analyzing comprises tracking theformation of at least one bubble.
 28. A method according to claim 1,wherein said analyzing estimating a diameter of at least one bubble. 29.A method according to claim 1, comprising estimating a physiologicalstate for diving purposes based on said analysis.
 30. A method accordingto claim 1, wherein transmitting comprises transmitting when in contactwith a skin surface.
 31. A method according to claim 1, whereinanalyzing comprises estimating a growth rate of bubbles.
 32. A methodaccording to claim 1, comprising estimating a physiological state basedon said analysis, in air or in outer space.
 33. A method according toclaim 1, comprising estimating a physiological state using multiplemeasured parameters, taking into account the interaction of theparameters.
 34. A method according to claim 33 wherein a change in oneor more physiological parameters in said measured parameters affects oneor more other parameters in said measured parameters.
 35. A methodaccording to claim 33 comprising verifying the integrity of saidestimating based on said interaction of the parameters.
 36. A methodaccording to claim 1, wherein transmitting comprises transmittingthrough clothes.
 37. A method according to claim 1, wherein transmittingcomprises transmitting through an optical transparent material.
 38. Amethod according to claim 1 comprising identifying a change of stresslevel in a user by identifying any one of, or combination of, a changein pulse rate, a change in respiratory rate, a change in systolic rate,or a change in cardiac output.
 39. A method of detecting gas bubbles ina living body, comprising: transmitting at least one original opticalsignal to a body portion; detecting a signal modulated by a flow ofblood in said body portion; and analyzing, using AM analysis, aperturbation in said signal to determine at least one of an existenceand a property of a bubble in said blood flow.
 40. A method according toclaim 39, comprising applying an FM analysis.
 41. Apparatus according toclaim 39, wherein said wave is optical and wherein said device isadapted to be worn on a human body.
 42. Apparatus according to claim 39,wherein said wave is optical and wherein said device is adapted forunderwater use during diving.
 43. A wearable apparatus for physiologicaltracking bubble detection, comprising: at least one electromagneticsignal source adapted to transmit an optical light wave into a body; atleast one sensor adapted to receive said signal after modulation by aflow in said body; and circuitry adapted to analyze said received signaland detect at least changes in at least two physiological parameters ofsaid body.
 44. Apparatus according to claim 43, wherein said at leasttwo physiological parameters are selected from a group comprising,existence of bubbles, heart rate, respiration rate, blood pressure,oxygen saturation and vascular response.